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Pulmonary embolism (PE) is a life-threatening medical condition caused by the thrombotic occlusion of one or more branches of the lung vasculature, which represents the third most common cause of cardiovascular mortality after myocardial infarction and stroke. PE treatment requires a tailored approach based on accurate risk stratification and personalized treatment decision-making. Anticoagulation is the cornerstone of PE management, yet patients at higher clinical risk may require more rapid reperfusion therapies. In recent years, transcatheter treatment has emerged as a valuable option for patients with intermediate-high or high-risk PE who have contraindications to systemic thrombolysis. Recent advancements in catheter-directed therapies, such as catheter-directed thrombolysis (CDT) and catheter-directed mechanical thrombectomy (CDMT), provide minimally invasive options for swift symptom relief and hemodynamic stabilization. This review aims to provide a practical approach for optimal patient selection and management for PE percutaneous therapies, supported by a thorough evaluation of the current evidence base supporting these procedures. A focus on post-procedural management, the prevention of recurrence, and monitoring for long-term complications such as chronic pulmonary hypertension and post-PE syndrome is also specifically tackled.

(1) Objective. The aim was to evaluate the risk of new exacerbations of heart failure (HF) in patients discharged from hospital emergency departments (EDs) without a structured HF follow-up. (2) Methods. This prospective, single-center cohort study included patients discharged from the ED following hospital admission for acute HF. The study analyzed the profile of patients seen in the ED and assessed their risk of new ED visits or HF-related hospitalizations within 12 months of discharge. (3) Results. A total of 779 patients were included, with a mean age of 82 ± 8 years; 471 were women (60.4%), and 674 (86.7%) had a history of prior HF episodes. Of these, 591 patients (76.1%) were referred to an unstructured HF follow-up in primary care (PC). Patients who experienced HF exacerbations within 12 months of ED discharge had a higher incidence of chronic kidney disease, elevated natriuretic peptide levels, and a higher number of prior HF exacerbations and were more likely to receive unstructured HF follow-up in PC. The presence of the last two factors was associated with the highest risk of HF exacerbation within 12 months of discharge (HR: 2.83; 95% CI: 1.60-5.03; p < 0.001). (4) Conclusions. Patients discharged from the ED after an HF episode and referred to PC without a structured HF follow-up have a high risk of ED revisits or rehospitalization for HF.

Background and Objectives: Previous studies showed that, paradoxically, obese patients with heart failure (HF) have better clinical outcomes compared to overweight, normal, or underweight patients. Scientific societies emphasize the importance of integrating quality of life (QoL) assessment in cardiovascular care. However, the association between QoL and weight remains understudied. Given the significant correlation between HF survival and QoL, it is essential to assess how obesity impacts patient-reported outcomes in this clinical setting. Methods: This cross-sectional multicenter study in 1028 HF patients with reduced ejection fraction (HFrEF) aims to evaluate the association between obesity and QoL, and whether the obesity paradox holds for HF patients regarding QoL. Specific and generic QoL questionnaires were administered alongside clinical parameters like body mass index (BMI) and body adiposity estimator (BAE). Results: Obese compared to non-obese reported worse QoL. In the adjusted linear regression models, neither BMI nor obesity were associated with QoL. Generalized additive models confirmed a strong non-parametric association between BMI, subdomain scores from Kansas City Cardiomyopathy Questionnaire (KCCQ) (OSS p = 0.004, CSS p = 0.006, TSS p = 0.02), and summary measurements of EQ-5D (EQ-5D index p = 0.003, visual analogue scale (VAS) p = 0.01). In contrast, BAE showed a statistically significant linear relation among QoL (OSS p ≤ 0.001, CSS p ≤ 0.001, TSS p ≤ 0.001) and EQ-5D summary measurements (EQ-5D index p ≤ 0.001, VAS p ≤ 0.001). Conclusions : Overall, obese patients have worse QoL; therefore, obesity cannot be considered a protective factor in terms of QoL in established HF.

Heart transplantation (HT) is the gold standard therapy for advanced heart failure (ADHF), and LVADs as destination therapy are an option in non-HT candidates. Most patients with ADHF never receive HT or an LVAD, so alternative strategies are needed. Intermittent levosimendan can reduce HF hospitalizations in ADHF patients in the short term. It is uncertain whether the results of the comparison of inotropes with older-generation LVADs would have the same outcomes in the current era of ADHF patients treated with levosimendan, who are less sick but older. In this paper, we compare the use of two therapeutic strategies for end-stage HF in patients who are not candidates for HT: repetitive intermittent levosimendan vs. LVAD as destination therapy. To do so, we compare two multicenter cohorts of real-life patients from Spain: the LEVO-D registry and the REGALAD registry. In total, 715 patients coming from the two registries were found: 403 from LEVO-D and 312 from REGALAD. Non-adjusted median survival was shorter for LEVO-D patients, with the benefit for the LVADs seen only after the first year of therapy. The survival advantage for the LVAD cohort was also true after analysis of the matched cohort but, as in the non-matched analysis, the survival benefit was mainly shown after one year of follow-up. We conclude that in elderly ADHF non-HT candidates, LVAD therapy offers significantly better long-term outcomes when compared to intermittent levosimendan; thus, it should be considered in carefully selected candidates. On the other hand, in poor LVAD candidates or highly comorbid patients, intermittent inotropic support with levosimendan could be a reasonable alternative to LVAD, as 1-year outcomes are similar.

Background/Objectives: Inherited arrhythmogenic syndromes comprise a heterogenic group of genetic entities that lead to malignant arrhythmias and sudden cardiac death. Genetic testing has become crucial to understand the disease etiology and allow for the early identification of relatives at risk; however, it requires an accurate interpretation of the data to achieve a clinically actionable outcome. This is particularly challenging for the large number of rare variants obtained by current high-throughput techniques, which are mostly classified as of unknown significance. Methods: In this work, we present a new algorithm for the genetic interpretation of the remaining rare variants in order to shed light on their potential clinical implications and reduce the burden of unknown significance. Results: Our study illustrates the potential utility of our individualized comprehensive stepwise analyses focused on the rare variants associated with IAS, which are currently classified as ambiguous, to further determine their trends towards pathogenicity or benign traits. Conclusions: We advocate for personalized disease-focused population frequency data and family segregation analyses for all rare variants that remain ambiguous to further clarify their role. The current ambiguity should not influence medical decisions, but a potential deleterious role would suggest a closer clinical follow-up and frequent genetic data review for a more personalized clinical approach.

Background: The prevention of thromboembolisms through anticoagulation and heart rate control is crucial in managing non-valvular atrial fibrillation (NVAF). This study aimed to analyze the consequences of poor anticoagulation control with vitamin K antagonists (VKAs) in Spanish patients with NVAF, focusing on thrombotic events, bleeding, mortality, healthcare resources (HRU), and costs. Methods: This observational, retrospective study used electronic medical records (BIG-PAC ® database) of NVAF patients who started VKA treatment between 1 January 2016 and 31 December 2018. Patients were followed up for two years and classified by poor or adequate anticoagulation control. Demographic and clinical characteristics, treatments, incidence of cardiovascular events, mortality rates, HRU, and costs were analyzed. Results: Patients with poor control ( n = 2136) had a 75% greater probability of suffering a cardiovascular event compared to patients with adequate control ( n = 2351) (HR, 1.75 [95%CI: 1.43-2.14; p < 0.001]). Cardiovascular events, major bleeding, minor bleeding, systemic thromboembolism, and ischemic strokes were reduced by 32.1%, 46.2%, 29.6%, 22.2%, and 16.1%, respectively. It was estimated that adequate anticoagulant control saved EUR 455/patient with NAVF due to reduced hospitalization for cardiovascular events. Conclusions: For VKA-treated NVAF patients, poor anticoagulation control was associated with a higher number of cardiovascular events, greater consumption of HRU, and higher management costs than for patients with adequate control.

Background: SGLT-2 inhibitors (SGLT-2is) are considered to be a first-line treatment for common conditions like type 2 diabetes, chronic kidney disease, and heart failure due to their proven ability to reduce cardiovascular and renal morbidity and mortality. Despite these benefits, SGLT-2is are associated with certain adverse effects (AEs), particularly genitourinary (GU) events, which can lead to treatment discontinuation in some patients. Preventing these AEs is essential for maintaining the cardiorenal benefits of SGLT-2is. Methods: A multidisciplinary panel of experts from various medical specialties reviewed the best available evidence on GU AEs associated with SGLT-2i therapy. The panel focused on the prevention and management of genital mycotic infections, urinary tract infections, and lower urinary tract symptoms in both the general population and high-risk groups, such as renal and cardiac transplant recipients. Results: The panel found that permanent discontinuation of SGLT-2is results in a rapid loss of cardiorenal benefits. Preventive strategies, including identifying high-risk patients before initiating therapy, are critical for minimizing GU AEs. Clinical trials show that most GU infections linked to SGLT-2i therapy are mild to moderate in severity and typically respond to standard antimicrobial treatment, without the need for discontinuation. Conclusions: Routine discontinuation of SGLT-2is due to GU AEs is not recommended. Therapy should be resumed as soon as possible, unless severe or persistent conditions contraindicate their use, in order to preserve the significant benefits of SGLT-2is in reducing cardiovascular and renal events.

SARS-CoV-2, the causative virus for the COVID-19 disease, uses its spike glycoprotein to bind to human ACE2 as a first step for viral entry into the cell. For this reason, great efforts have been made to find mechanisms that disrupt this interaction, avoiding the infection. Nitric oxide (NO) is a soluble endogenous gas with known antiviral and immunomodulatory properties. In this study, we aimed to test whether NO could inhibit the binding of the viral spike to ACE2 in human cells and its effects on ACE2 enzymatic activity. Our results show that ACE2 activity was decreased by the NO donors DETA-NONOate and GSNO and by the NO byproduct peroxynitrite. Furthermore, we found that DETA-NONOate could break the spike-ACE2 interaction using the spike from two different variants (Alpha and Gamma) and in two different human cell types. Moreover, the same result was obtained when using NO-producing murine macrophages, while no significant changes were observed in ACE2 expression or distribution within the cell. These results support that it is worth considering NO as a therapeutic agent for COVID-19, as previous reports have suggested.

Objectives : Mitral regurgitation (MR) is the second most common valve disease in Europe, and differences between men and women have been described in relation to aetiology or management, which might impact the decision for intervention and patients' clinical and economic outcomes. Thus, the objective was to analyse the burden of MR in Spain by aetiology and sex, and the management of all patients suffering from MR being admitted to hospital between 2016-2021. Methods : An analysis was carried out with the Ministry of Health's database, including all patients in public and subsidised hospitals and defining two groups, general MR and those patients undergoing Transcatheter Edge-to-Edge repair (TEER), using a descriptive analysis of patients' characteristics, use of resources, and outcomes; standardised rates were calculated and observed outcomes were described. Results : Hospital admissions increased from 2016 ( n = 32,806) to 2021 (total n = 61,036). In general, the women were older and presented more complications. The majority of patients suffered from degenerative MR (DMR) ( n = 183,005, 59.55%), and 61.56% were women, contrary to functional MR (FMR) ( n = 124,278), which consisted of 62.15% males. In total, 1,689 TEERs were performed, 23.33% of them in urgent admissions, and mostly in men (65.66%). All groups showed higher rates of intervention for males. Regarding costs, women presented lower mean costs in the general MR groups but those undergoing TEER presented, in all cases, costs higher than men. Conclusions : MR entails a significant burden for patients and the Spanish healthcare system, increasing over the period of study. Differences in aetiologies by sex have been found in patients' characteristics as well as outcomes. Further studies are needed to optimise patients' management and their outcomes in relation to sex and aetiology.

Background: Complications in community-acquired pneumonia (CAP), including cardiovascular events (CVE), can occur during an acute episode and in the long term. We aimed to analyse the role of endothelial damage biomarkers (C-terminal endothelin-1 precursor fragment [CT-proET-1] and mid-regional pro-adrenomedullin [MR-proADM]), in contrast to classic inflammation markers (C Reactive Protein [CRP] and procalcitonin [PCT]) in patients admitted for CAP and their relationship with ICU admission, CVE and mortality in the short and long term; Methods: Biomarkers were analysed in 515 patients with CAP at day 1, 285 at day 5 and 280 at day 30. Traditional inflammatory biomarkers and endothelial damage biomarkers were measured. ICU admission, CVE and mortality (in-hospital and 1-year follow-up) were assessed using receiver operating characteristic (ROC) curve analysis and univariate logistic regression. Results: A statistically significant association was observed between initial, raised CT-proET-1 and MR-proADM levels, the need for ICU admission and the development of in-hospital CVE or in-hospital mortality. Both endothelial markers maintained a strong association at day 30 with 1-year follow-up CVE. At day 1, CRP and PCT were only associated with ICU admission. On day 30, there was no association between inflammatory markers and long-term CVE or death. The odds ratio (OR) and area under the curve (AUC) of endothelial biomarkers were superior to those of classic biomarkers for all outcomes considered. Conclusions: Endothelial biomarkers are better indicators than classic ones in predicting worse outcomes in both the short and long term, especially CVE. MR-proADM is the best biomarker for predicting complications in CAP.

Background/Objectives: We assessed the effectiveness and safety of vitamin K antagonists (VKAs) versus direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) using artificial intelligence techniques. Methods: This is a retrospective study in 15 Spanish hospitals (2014-2020), including adult AF patients with no history of anticoagulation, thrombosis events, rheumatic mitral valvular heart disease, mitral valve stenosis, or pregnancy. We employed EHRead ® technology based on natural language processing (NLP) and machine learning (ML), along with SNOMED-CT terminology, to extract clinical data from electronic health records (EHRs). Using propensity score matching (PSM), the effectiveness, safety, and hospital mortality of VKAs versus DOACs were analyzed through Kaplan-Meier curves and Cox regression. Results: Out of 138,773,332 EHRs from 4.6 million individuals evaluated, 44,292 patients were included, 79.6% on VKAs and 20.4% on DOACs. Most patients were elderly [VKA 78 (70, 84) and DOAC 75 (66, 83) years], with numerous comorbidities (75.5% and 70.2% hypertension, 47.2% and 39.9% diabetes, and 40.3% and 34.8% heart failure, respectively). Additionally, 60.4% of VKA and 48.7% of DOAC users had a CHA2DS2-VASc Score ≥4. After PSM, 8929 patients per subgroup were selected. DOAC users showed a lower risk of thrombotic events [HR 0.81 (95% CI 0.70-0.94)], minor bleeding [HR 0.89 (95% CI 0.83-0.96)], and mortality [HR 0.80 (95% CI 0.69-0.92)]. Conclusions: Applying NLP and ML, we generated valuable real-world evidence on anticoagulated AF patients in Spain. Even in complex populations, DOACs have demonstrated a better safety and effectiveness profile than VKAs.

Background/Objectives: Heart failure worsens the prognosis of patients with infective endocarditis (IE) and is mainly caused by severe valvular regurgitation. The aim of our investigation is to describe the clinical, epidemiological, microbiological, and echocardiographic characteristics of patients with native left-sided infective endocarditis (NLSIE) with severe valvular regurgitation; to describe the prognosis according to the therapeutic approach; and to determine the prognostic factors of in-hospital mortality. Methods : We prospectively recruited all episodes of possible or definite NLSIE diagnosed at three tertiary hospitals between 2005 and 2022. Patients were divided into two groups: patients with severe valvular regurgitation at the time of admission or during hospitalization and patients without severe valvular regurgitation. We analyzed up to 85 variables concerning epidemiological, clinical, analytical, microbiological, and echocardiographic data. Results : We recovered 874 patients with NLSIE, 564 (65%) of them with severe valvular regurgitation. There were no differences in mortality among patients with and without severe regurgitation (30.2% vs. 26.5%, p = 0.223). However, mortality increased when patients with severe regurgitation developed heart failure (33% vs. 11.4%, p < 0.001). Independent factors related to heart failure were age (OR 1.02 [1.01-1.034], p = 0.001), anemia (OR 1.2 [1.18-3.31], p = 0.01), atrial fibrillation (OR 2.3 [1.08-4.89], p = 0.03), S. viridans -related IE (OR 0.47 [0.3-0.73], p = 0.001), and mitroaortic severe regurgitation (OR 2.4 [1.15-5.02], p = 0.019). Conclusions : Severe valvular regurgitation is very frequent among patients with NLSIE, but it does not worsen the prognosis of patients unless complicated with heart failure.

The primary objective of this study was to conduct a cost-utility analysis of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in real-world, comparing their use with standard care for managing cardiovascular disease. A multicenter prospective study was conducted across 12 Spanish hospitals from May 2020 to April 2022, involving 158 patients with hypercholesterolemia or atherosclerotic cardiovascular disease. This study assessed health-related quality of life (QoL) using the EQ-5D-3L questionnaire. The cost-utility analysis evaluated the economic impact of PCSK9 inhibitors when used with standard care compared to standard care alone, calculating the incremental cost-effectiveness ratio (ICER). This study included 158 patients with an average age of 61 years, male (66.5%). For patients initiating PCSK9 inhibitors, the treatment cost was EUR 13,633.39, while standard therapy cost EUR 3638.25 over two years. QoL for PCSK9 inhibitors stood at 1.6489 over two years, compared to 1.4548 for standard therapy. The results revealed favorable cost-utility outcomes, with an ICER of EUR 51,427.72. Significant improvements were observed in the domains of mobility, self-care, daily activities, pain/discomfort, and anxiety/depression ( p < 0.001). This study presents the first real-world cost-utility analysis of PCSK9 inhibitors, supporting their economic rationale and highlighting their benefits in clinical practice. Healthcare decision-makers can use these results to inform their decisions and reimbursement policies concerning PCSK9 inhibitors. Trial Registration clinicaltrials.gov Identifier: NCT04319081.

NADPH oxidases (NOXs) have been described as critical players in vascular remodeling, a mechanism modulated by matrix metalloproteinases. In this study, we describe for the first time the upregulation of MMP-10 through the activation of NOX5 in endothelial cells. In a chronic NOX5 overexpression model in human endothelial cells, MMP-10 production was measured at different levels: extracellular secretion, gene expression (mRNA and protein levels), and promoter activity. Effects on cell migration were quantified using wound healing assays. NOX5 overexpression increased MMP-10 production, favoring cell migration. In fact, NOX5 and MMP-10 silencing prevented this promigratory effect. We showed that NOX5-mediated MMP-10 upregulation involves the redox-sensitive JNK/AP-1 signaling pathway. All these NOX5-dependent effects were enhanced by angiotensin II (Ang II). Interestingly, MMP-10 protein levels were found to be increased in the hearts of NOX5-expressing mice. In conclusion, we described that NOX5-generated ROS may modulate the MMP-10 expression in endothelial cells, which leads to endothelial cell migration and may play a key role in vascular remodeling.

Atrial fibrillation (AF), the most common arrhythmia, is associated with increased morbidity, mortality, and healthcare costs. Evidence indicates that rhythm control offers superior cardiovascular outcomes compared to rate control, especially when initiated early after the diagnosis of AF. Catheter ablation remains the single best therapy for AF; however, it is not free from severe complications and only a small percentage of AF patients in the Western world ultimately receive ablation. Ensuring that AF ablation is safe, effective, and efficient is essential to make it accessible to all patients. With the limitations of traditional thermal ablative energies, pulsed field ablation (PFA) has emerged as a novel non-thermal energy source. PFA targets irreversible electroporation of cardiomyocytes to achieve cell death without damaging adjacent structures. Through its capability to create rapid, selective lesions in myocytes, PFA presents a promising alternative, offering enhanced safety, reduced procedural times, and comparable, if not superior, efficacy to thermal energies. The surge of new evidence makes it challenging to stay updated and understand the possibilities and challenges of PFA. This review aims to summarize the most significant advantages of PFA and how this has translated to the clinical arena, where four different catheters have received CE-market approval for AF ablation. Further research is needed to explore whether adding new ablation targets, previously avoided due to risks associated with thermal energies, to pulmonary vein isolation can improve the efficacy of AF ablation. It also remains to see whether a class effect exists or if different PFA technologies can yield distinct clinical outcomes given that the optimization of PFA parameters has largely been empirical.

Electrophysiological aspects of cardiac amyloidosis (CA) are still poorly explored compared to other aspects of the disease. However, electrocardiogram (ECG) abnormalities play an important role in CA diagnosis and prognosis and the management of arrhythmias is a crucial part of CA treatment. Low voltages and a pseudonecrosis pattern with poor R-wave progression in precordial leads are especially common findings. These are useful for CA diagnosis and risk stratification, especially when combined with clinical or echocardiographic findings. Both ventricular and supraventricular arrhythmias are common in CA, especially in transthyretin amyloidosis (ATTR), and their prevalence is related to disease progression. Sustained and non-sustained ventricular tachycardias' prognostic role is still debated, and, to date, there is a lack of specific indications for implantable cardiac defibrillator (ICD). On the other hand, atrial fibrillation (AF) is the most common supraventricular arrhythmia with a prevalence of up to 88% of ATTR patients. Anticoagulation should be considered irrespective of CHADsVA score. Furthermore, even if AF seems to not be an independent prognostic factor in CA, its treatment for symptom control is still crucial. Finally, conduction disturbances and bradyarrhythmias are also common, requiring pacemaker implantation in up to 40% of patients.

Despite the plasma proteome being able to provide a unique insight into the health and disease status of individuals, holding singular promise as a source of protein biomarkers that could be pivotal in the context of personalized medicine, only around 100 proteins covering a few human conditions have been approved as biomarkers by the US Food and Drug Administration (FDA) so far. Mass spectrometry (MS) currently has enormous potential for high-throughput analysis in clinical research; however, plasma proteomics remains challenging mainly due to the wide dynamic range of plasma protein abundances and the time-consuming procedures required. We applied a new MS-based multiplexed proteomics workflow to quantitate proteins, encompassing 67 FDA-approved biomarkers, in >1300 human plasma samples from a clinical cohort. Our results indicate that this workflow is suitable for large-scale clinical studies, showing good accuracy and reproducibility (coefficient of variation (CV) < 20 for 90% of the proteins). Furthermore, we identified plasma signature proteins (stable in time on an individual basis), stable proteins (exhibiting low biological variability and high temporal stability), and highly variable proteins (with low temporal stability) that can be used for personalized health monitoring and medicine.

Background/objectives: The direct bridge to urgent heart transplant (HT) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support has been associated with high morbidity and mortality. The objective of this study is to analyze the morbidity and mortality of patients transplanted with VA-ECMO and compare the presumed differences between various eras over a 17-year timeline., Methods: This is a prospective, observational study on consecutive patients stabilized with VA-ECMO and transplanted with VA-ECMO from July 2007 to December 2023 at a reference center (98 patients). Objective variables were mortality and morbidity from renal failure, venous thromboembolic disease (VTD), primary graft dysfunction (PGD), the need for tracheostomy, severe myopathy, reoperation, post-transplant ECMO, vascular complications, and sepsis/infection., Results: The percentage of patients who reached transplantation without the need for mechanical ventilation has increased over the periods studied. No significant differences were found between the study periods in 30-day mortality ( p = 0.822), hospital discharge ( p = 0.972), one-year mortality ( p = 0.706), or five-year mortality ( p = 0.797). Survival rates in these periods were 84%, 75%, 64%, and 61%, respectively. Comorbidities were very frequent, with an average of 3.33 comorbidities per patient. The most frequent were vascular complications (58%), the need for post-transplant ECMO (57%), and myopathy (55%). The development of myopathy and the need for post-transplant ECMO were higher in recent periods ( p = 0.004 and p = 0.0001, respectively)., Conclusions: VA-ECMO support as a bridge to HT allows hospital discharge for 3 out of 4 transplanted patients. This survival rate has not changed over the years. The comorbidities associated with this device are frequent and significant.

Current cardiovascular prevention guidelines emphasise considering sex, gender, and gender identity in risk assessment. This study evaluated the impact of lifestyle habits and chronic diseases on cardiovascular mortality risk in women over 50 with high vascular risk and developed a predictive model for menopausal women with cardiovascular risk factors. A retrospective cohort study used data from the 2011 Spanish National Health Survey and the national death register, focusing on menopausal and postmenopausal women without prior cardiovascular events but with at least one major risk factor. Participants were followed for up to 10 years, assessing mortality from circulatory system diseases and other causes. Exposure variables included socio-demographics, lifestyle habits, health status, self-perceived health, health service use, and pharmacological treatments. Of the 21,007 respondents, 3057 women met the inclusion criteria. The 10-year cumulative incidence of mortality from circulatory causes was 5.9%, and from other causes, 12.7%. Independent predictors of cardiovascular mortality were never consuming legumes, poor self-perceived health, diabetes treatment, lack of physical activity, and older age. Lipid-lowering treatment was protective. The model demonstrated good fit and predictive capacity (C-index = 0.773). This study highlights the significant influence of physical activity, legume consumption, self-perceived health, and specific treatments on cardiovascular mortality risk in menopausal women.

Objective : We analyzed the obstetric and cardiac characteristics and results of pregnant women with heart disease (HD) and compared their results with those of healthy controls. Methods : In this retrospective single-center case-control study, women with HD attended between 2010 and 2018 were matched at a 1:2 ratio (according to date of delivery, parity, and singleton or twin pregnancy) with controls without heart disease treated in the same referral center. Results : We identified 141 pregnant women with HD, of whom 132 reached 22 weeks of gestation and were paired with 264 healthy controls, for a total of 396 participants and 408 newborns. Most common HDs were congenital HD (53 women), arrhythmia (46), valvular HD (35), and cardiomyopathy (16), having women with more than one coexisting HD. During pregnancy or the puerperium, 19.9% of mothers experienced a major adverse cardiac event (MACE), with 5% requiring intensive care unit (ICU) admission. The rates of cesarean section were 37.1% in the case group and 18.2% in the control group, with an odds ratio (OR) of 2.66 (95% CI = 1.66-4.26, p < 0.001). We also found a higher use of general anesthesia, with an OR of 10.73 (95% CI = 2.32-49.75, p = 0.002); more prolonged hospitalizations, with an OR of 2.91 (95% CI 1.02-8.35, p = 0.023); and a higher incidence of low neonatal weight, with an OR of 1.96 (95% CI 1.09-3.52, p = 0.012). There were no differences between groups in terms of gestational age at delivery; however, we observed greater prematurity in women with HD, without reaching statistical significance. The rate of congenital heart disease among the newborns of mothers with HD was 13.2%. Conclusions : HD increases maternal morbidity during pregnancy and it is associated with higher rates of cesarean section and low birth weight.

Background: Physical activity (PA) intensity could play a key role in atherosclerosis risk, but the existing literature shows controversial results. The aim of this study was to analyze the association of different PA levels with the presence of subclinical atherosclerosis in femoral and carotid arteries. Methods: A cross-sectional analysis was conducted of 449 middle-aged men belonging to the Aragon Workers' Health Study. Demographic, anthropometric, and clinical data were obtained during the annual medical examination. Ultrasonography was used to assess the presence of atheroma plaques in femoral and carotid territories. Accelerometry was used to assess habitual PA. Participants were categorized into vigorous PA (VPA) groups (0 min/week, >0-60 min/week, >60 min/week), and into moderate to vigorous PA (MVPA) groups using terciles as cut-offs. Results: Compared with participants who completed 0 min/week of VPA, those participants who completed >60 min/week of VPA had fully adjusted odds of subclinical atherosclerosis of 0.47 (95%CI: 0.22, 0.99, p < 0.05) and 0.35 (95%CI: 0.17, 0.73, p < 0.05) for femoral and any territory (femoral and/or carotid) respectively. No significant differences were observed in the prevalence of atheroma plaques in any vascular territory between the different MVPA groups. Conclusions: Performing more than 60 min/week of VPA is associated with reduced odds for subclinical atherosclerosis in femoral or any vascular territory in adult men.

Background: ATTR-CM is becoming more prevalent, and disease-modifying therapy has been investigated in recent years with promising results. Diflunisal has shown TTR-stabilizing properties assessed by biomarkers and echocardiography, but there are no trials addressing the evolution of morphological changes with CMR. Methods and Results: AMILCA-DIFLU is an exploratory pilot study prospective, single-center, non-randomized, open-label clinical trial. Patients diagnosed with ATTR-CM underwent clinical, functional, biochemical and imaging assessment before and one year after diflunisal therapy initiation. Of the twelve ATTR-CM patients included, only nine patients completed treatment and study protocol in 12 months. To increase the sample size, we included seven real-world patients with one year of diflunisal treatment. Among the group of patients who completed treatment, diflunisal therapy did not show improvement in cardiac disease status as assessed by many cardiac and inflammatory biomarkers, 6MWT and CMR parameters after one year of treatment. However, a non-significant trend towards stabilization of CMR parameters such as LVEF, ECV and T2 at one year was found. When comparing the group of patients who completed diflunisal therapy and those who did not, a significant decrease in the distance performed in the 6MWT was found in the group of patients who completed treatment at one year (-14 ± 81.8 vs. -173 ± 122.2; p = 0.032). Diflunisal was overall well tolerated, showing only a statistically significant worsening in renal function in the group of diflunisal-treatment patients with no clinical relevance or need for treatment discontinuation. Conclusions: In patients with ATTR-CM, treatment with diflunisal was overall well tolerated and tended to stabilize or slow down amyloid cardiac disease progression assessed by CMR parameters, cardiac and inflammatory biomarkers and functional capacity.

Lymphedema presents significant challenges to patients' quality of life, prompting the exploration of innovative treatments, such as collagen scaffolds, aimed at treating and reducing the risk of lymphedema. We aimed to evaluate the preventive and therapeutic efficacy and the lymphangiogenic potential of implanted aligned nanofibrillar collagen scaffolds (BioBridge TM ) following the induction of secondary lymphedema in a rabbit model. Thirty rabbits were divided into treatment (G1), prevention (G2), and control (G3) groups. Secondary lymphedema was induced in all groups. BioBridge TM implantation was performed in G2 and G1 on days 0 and 60, respectively. Follow-ups included hindlimb circumference measurements and indocyanine green lymphography at 0, 60, and 90 days. None of the study rabbits exhibited dermal backflow on day 0 before surgery. At 60 days, the incidence rates of dermal backflow in G1, G2, and G3 were 100%, 44.4%, and 90%, respectively. Furthermore, at 90 days, the incidence rates were 22.2%, 44.4%, and 90%, respectively. New linear lymphatic observation was seen in rabbits with resolved dermal backflow. The findings of this study demonstrated the capacity of BioBridge TM scaffolds to induce new lymphatic vessel formation and reduce dermal backflow in secondary lymphedema in a rabbit model.

Background/Objectives : Coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM) are characterized by chronic low-grade inflammation. However, measuring cytokines typically involves invasive blood sampling, which can be problematic for CAD patients. This study aimed to assess ophthalmological parameters and tear cytokines in patients with CAD, comparing those with comorbid T2DM to those without to understand their inflammatory profiles. Methods : One hundred subjects with suspected chronic or acute CAD were initially included in this single-center cross-sectional study after clinical stabilization. Seventy-two patients with confirmed CAD were divided into two groups: 32 patients with T2DM and 40 patients without T2DM. A total of 144 eyes were examined, and tear fluid samples were collected to determine cytokine concentrations. Ophthalmological parameters and tear concentrations of cytokines were analyzed, controlling for age, sex, and other cardiovascular risk factors. Results : Patients with CAD and T2DM exhibited decreased ophthalmological parameters and increased cytokine concentrations in comparison to those without T2DM. Significant inverse correlations between ophthalmological parameters and cytokine concentrations were observed. Following adjustment, a full logistic regression model for distinguishing patients with CAD and comorbid T2DM included macular cube volume, mean macular thickness, interleukin (IL)-4, IL-5, IL-6, IL-8, IL-9, IL-13, granulocyte colony-stimulating factor (G-CSF), CCL3, CCL4, and CCL11/eotaxin-1, demonstrating excellent discriminatory power (Area Under the Curve = 0.95, 95% Confidence Interval = 0.91-0.99; p < 0.001). Subsequently, IL-5 (Odds Ratio = 1.68, 95% CI = 1.26-2.24; p < 0.001), G-CSF (OR = 1.06, 95% CI = 1.02-1.11; p < 0.01), and CCL11/eotaxin-1 (OR = 1.56, 95% CI = 1.19-2.05; p = 0.001) emerged as the most distinguishing variables in a reduced model (AUC = 0.89, 95% CI = 0.84-0.95; p < 0.001). Conclusions : Differences in ophthalmological variables, mainly in cytokine concentrations, suggest distinct pathophysiological mechanisms in patients with CAD based on the presence of T2DM. These findings demonstrate that the inflammatory profile can be readily detected through tear sample cytokines, proving valuable for establishing more accurate prognoses and monitoring in cardiometabolic disorders.

The improvement in survival rates in pediatric malignancies has led to an increase in the number of cancer survivors who are at risk of developing cardiotoxicity and heart failure. Cardiac dysfunction in these patients can occur asymptomatically, and the diagnosis in a symptomatic phase is associated with reduced treatment response and worse prognosis. For this reason, it is essential to establish protocols to follow up on these patients and identify those at risk of cardiotoxicity in order to start early and effective therapies. This review aims to summarize the latest findings in the diagnosis and treatment of cancer therapy-related cardiac disease in long-term survivors of childhood cancer, with a focus on heart failure.

Background . Iron deficiency (ID) is a significant, high-prevalence comorbidity in chronic heart failure (HF) that represents an independent predictor of a worse prognosis. However, a clear-cut diagnosis of ID in HF patients is not assured. The soluble transferrin receptor (sTfR) is a marker that reflects tissue-level iron demand and may be an early marker of ID. However, the impact of sTfR levels on clinical outcomes in non-anemic HF patients with a normal systemic iron status has never been evaluated. Methods . This is a post hoc analysis of an observational, prospective cohort study of 1236 patients with chronic HF of which only those with normal hemoglobin levels and a normal systemic iron status were studied. The final cohort consisted of 215 patients. Tissue ID was defined as levels of sTfR > 75th percentile (1.65 mg/L). Our aim was to describe the association between sTfR and clinical outcomes (all-cause death and HF hospitalization) and to explore its association with a wide array of serum biomarkers. Results . The sTfR level (HR 1.48, 95% CI 1.13-1.96, p = 0.005) and tissue ID (HR 2.14, 95% CI 1.22-3.75, p = 0.008) was associated with all-cause death. However, we found no association between sTfR levels and the risk of HF hospitalization. Furthermore, high sTfR levels were associated with a worse biomarker profile indicating myocardial damage (troponin and NT-proBNP), systemic inflammation (CRP and albumin), and impaired erythropoiesis (erythropoietin). Conclusions. In this cohort, the presence of tissue ID defined by sTfR levels is an independent factor for all-cause death in patients with normal systemic iron parameters.

Arrhythmogenic cardiomyopathy is an inherited entity characterized by irregular cell-cell adhesion, cardiomyocyte death and fibro-fatty replacement of ventricular myocytes, leading to malignant ventricular arrythmias, contractile dysfunction and sudden cardiac death. Pathogenic variants in genes that encode desmosome are the predominant cause of arrhythmogenic cardiomyopathy. Moreover, signalling pathways such as Wnt/ß-catenin and transforming growth factor-β have been involved in the disease progression. However, still little is known about the molecular pathophysiological mechanisms that underlie arrhythmogenic cardiomyopathy pathogenesis. We used mRNA and small RNA sequencing to analyse the transcriptome of health and arrhythmogenic cardiomyopathy of autopsied human hearts. Our results showed 697 differentially expressed genes and eight differentially expressed miRNAs. Functional enrichment revealed mitochondrial respiratory-related pathways, impaired response to oxidative stress, apoptotic signalling pathways and inflammatory response-related and extracellular matrix response pathways. Furthermore, analysis of the miRNA-mRNA interactome identified eleven negatively correlated miRNA-target pairs for arrhythmogenic cardiomyopathy. Our finding revealed novel arrhythmogenic cardiomyopathy-related miRNAs with important regulatory function in disease pathogenesis, highlighting their value as potential key targets for therapeutic approaches.

Over the past five decades, the Fontan procedure has been developed to improve the life expectancy of patients with congenital heart defects characterized by a functionally single ventricle. The Fontan circulation aims at redirecting systemic venous return to the pulmonary circulation in the absence of an impelling subpulmonary ventricle, which makes this physiology quite fragile and leads to several long-term complications. Despite the importance of hemodynamic assessment through cardiac catheterization in the management and follow-up of these patients, a thorough understanding of the ultimate functioning of this type of circulation is lacking, and the interpretation of the hemodynamic data is often complex. In recent years, new tools such as combined catheterization with cardiopulmonary exercise testing have been incorporated to improve the understanding of the hemodynamic profile of these patients. Furthermore, extensive percutaneous treatment options have been developed, addressing issues ranging from obstructive problems in Fontan pathway and acquired shunts through compensatory collaterals to the percutaneous treatment of lymphatic circulation disorders and transcatheter edge-to-edge repair of atrioventricular valves. The aim of this review is to detail the various tools used in cardiac catheterization for patients with Fontan circulation, analyze different percutaneous treatment strategies, and discuss the latest advancements in this field.

Background: Longitudinal data on reverse cardiac remodeling and outcomes after transcatheter edge-to-edge repair (TEER) are limited., Methods: A total of 78 patients with severe mitral regurgitation (MR) were included retrospectively. All patients had echocardiography at baseline and again six months after TEER. They were monitored for a primary composite endpoint, consisting of heart failure hospitalization and cardiovascular death, over 13 months., Results: Significant decreases in the left ventricular ejection fraction (LVEF), all myocardial work indices (except global wasted work), and the left atrial reservoir were observed after TEER. Additionally, there was a decrease in the pulmonary artery systolic pressure and an increase in the tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio. A post-TEER TAPSE/PASP ratio of <0.47 (HR: 4.76, p -value = 0.039), and a post-TEER left atrial reservoir of <9.0% (HR: 2.77, p -value = 0.047) were associated with the primary endpoint., Conclusions: Echocardiography post-TEER reflects impairment in ventricular performance due to preload reduction and right ventricle and pulmonary artery coupling improvement. Short-term echocardiography after TEER identifies high-risk patients who could benefit from a close clinical follow-up. The prognostic significance of LA strain and the TAPSE/PASP ratio should be validated in subsequent large-scale prospective studies.

Background . Despite technical advancements, patients with sequential or diffuse coronary lesions undergoing percutaneous coronary intervention (PCI) have an increased risk of cardiovascular events at follow-up. We aimed to analyze the utility of a SyncVision/iFR (S-iFR)-guided PCI strategy versus an angiography-guided strategy in patients with this type of lesions. Methods . Randomized, multicenter, controlled, and open-label trial to compare S-iFR versus angiography-guided PCI in patients with sequential or diffuse angiographic coronary stenosis (ClinicalTrials.gov identifier: NCT04283734). The primary endpoint was the implanted stent length. The main secondary endpoint was targeting vessel failure (TVF) at one year. Results . A total of 100 patients underwent randomization, with 49 patients assigned to the S-iFR group and 51 to the angiography-guided PCI group. There were no differences between groups regarding clinical and anatomical characteristics. The baseline iFR was 0.71 ± 0.16 vs. 0.67 ± 0.19 ( p = 0.279) in the S-iFR and angiography group, respectively. The mean lesion length was 42.3 ± 12 mm and 39.8 ± 12 ( p = 0.297). The implanted stent length was 32.7 ± 17.2 mm in the S-iFR group and 43.1 ± 14.9 mm in the angiography group (mean difference, -10.4 mm; 95% confidence interval [CI], -16.9 to -4.0; p = 0.002). At one year, target vessel failure (TVF) occurred in four patients: three (6.1%) in the S-iFR group vs. one (1.9%) in the angiography group ( p = 0.319). Conclusions . Among patients with sequential or long diffuse coronary lesions, a S-iFR-guided PCI strategy resulted in a reduction of the total stent length compared to an angiography-guided PCI strategy. A nonsignificant increase in TVF was observed in the S-iFR group.

Introduction : Non-ischemic dilated cardiomyopathy (NIDCM) is characterized by a reduced left ventricular (LV) ejection fraction (LVEF, <50%) and a high risk for heart failure (HF) and death. Echocardiography-derived hemodynamic forces (HDFs) may provide important information on LV mechanics, but their prognostic value is unknown. Aim : To explore the features of echocardiography-derived HDFs in NIDCM and their association with clinical endpoints. Methods : Asymptomatic, non-hospitalized NIDCM patients free from coronary artery disease and moderate or severe valvular heart disease were included in this single-center observational retrospective longitudinal study. Those with atrial fibrillation and a follow-up <12 months were excluded. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death, HF hospitalization, and ambulatory intravenous diuretics administration. LV HDFs were analyzed with a prototype software. Apex-base (HDFs-ab), lateral-septal (HDFs-ls), and HDFs-angle were computed. Results : Ninety-seven patients were included, sixty-seven (69%) were males, mean age was 62 ± 14 years, and mean LVEF was 39.2 ± 8.6%. During a median follow-up of 4.2 (3.1-5.1) years, 19 (20%) patients experienced MACE. These patients had a higher HDFs-angle (71.0 (67.0-75.0) vs. 68.0 (63.0-71.0)°, p = 0.005), lower HDFs-ls (1.36 (1.01-1.85) vs. 1.66 ([1.28-2.04])%, p = 0.015), but similar HDFs-ab (5.02 (4.39-6.34) vs. 5.66 (4.53-6.78)%, p = 0.375) compared to those without MACE. in a Cox regression analysis, HDFs-angle (HR 1.16 (95%-CI 1.04-1.30), p = 0.007) was associated with MACE, while other conventional echocardiography parameters, including LVEF and LV longitudinal strain, were not. Conclusions : HDFs-angle is associated with clinical endpoints in NIDCM. A higher HDFs-angle may be a marker of impaired myocardial performance in patients with reduced LVEF.

Background: In arrhythmogenic right ventricular cardiomyopathy (ARVC) non-invasive scar evaluation is not included among the diagnostic criteria or the predictors of ventricular arrhythmias (VA) and sudden death (SD). Computed tomography (CT) has excellent spatial resolution and allows a clear distinction between myocardium and fat; thus, it has great potential for the evaluation of myocardial scar in ARVC. Objective: The objective of this study is to evaluate the feasibility, and the diagnostic and prognostic value of semi-automated quantification of right ventricular (RV) fat replacement from CT images. Methods: An observational case-control study was carried out including 23 patients with a definite (19) or borderline (4) ARVC diagnosis and 23 age- and sex-matched controls without structural heart disease. All patients underwent contrast-enhanced cardiac CT. RV images were semi-automatically reconstructed with the ADAS-3D software (ADAS3D Medical, Barcelona, Spain). A fibrofatty scar was defined as values of Hounsfield Units (HU) <-10. Within the scar, a border zone (between -10 HU and -50 HU) and dense scar (<-50 HU) were distinguished. Results: All ARVC patients had an RV scar and all scar-related measurements were significantly higher in ARVC cases than in controls ( p < 0.001). The total scar area and dense scar area showed no overlapping values between cases and controls, achieving perfect diagnostic performance (sensitivity and specificity of 100%). Among ARVC patients, 16 (70%) had experienced sustained VA or aborted SD. Among all clinical, ECG and imaging parameters, the dense scar area was the only one with a statistically significant association with VA and SD ( p = 0.003). Conclusions: In ARVC, RV myocardial fat quantification from CT is feasible and may have considerable diagnostic and prognostic value.

Transcatheter aortic valve implantation (TAVI) now represents the mainstay of treatment for severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as the cornerstone. Leveraging data from multiple randomized controlled trials, the current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without or with atrial fibrillation, respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment.

Limited molecular data exist on the prevalence and subtype distribution of Blastocystis spp., the most prevalent parasite in human and animal feces worldwide. A total of 44 different subtypes (STs) of Blastocystis are currently recognized based on the sequence of the small subunit ribosomal RNA ( SSU-rRNA ) gene. This is a molecular study of Blastocystis spp. in hospitalized patients with gastrointestinal symptoms in northern Spain. We analyzed 173 Blastocystis -positive patients with gastrointestinal symptoms by using nested PCR for molecular detection, subtype identification, phylogenetic analyses, and genetic diversity assessment. ST2 (34.1%) and ST3 (34.7%) predominated, followed by ST1 (15.6%) and ST4 (15.6%). Mixed infections with different subtypes were observed in some patients. Sequence analysis revealed for the first time in European humans the allele 88 (a variant of ST1). In other cases, alleles commonly found in animal samples were detected (allele 9 in ST2, allele 34 in ST3, and allele 42 in ST4). Phylogenetic analysis showed high variability in ST1 and ST2, suggesting a polyphyletic origin, while both ST3 and ST4 exhibited higher genetic homogeneity, indicating a possible monophyletic origin and recent transmission to humans. These data confirm Blastocystis spp. subtype diversity and may help in understanding the evolutionary processes and potential zoonotic transmission of this parasite.

Background: Transthyretin cardiac amyloidosis (ATTR amyloidosis) is a frequent etiology of heart failure. Inflammation and mineral metabolism are associated with myocardial dysfunction and clinical performance. Cardiac global longitudinal strain (GLS) allows function assessment and is associated with prognosis. Our aim was to describe possible correlations between GLS, biomarker levels and clinical performance in ATTR amyloidosis., Methods: Thirteen patients with ATTR amyloidosis were included. Clinical characteristics; echocardiographic features, including strain assessment and 6 min walk test (6MWT); and baseline inflammatory, mineral metabolism and cardiovascular biomarker levels were assessed., Results: Of the 13 patients, 46.2% were women, and the mean age was 79 years. TAPSE correlated with NT-ProBNP (r -0.65, p < 0.05) and galectin-3 (r 0.76, p < 0.05); E/E' ratio correlated with hsCRP (r 0.58, p < 0.05). Left ventricular GLS was associated with NT-ProBNP (r 0.61, p < 0.05) (patients have a better prognosis if the strain value is more negative) and left atrial GLS with NT-ProBNP (r -0.73, p < 0.05) and MCP1 (r 0.55, p < 0.05). Right ventricular GLS was correlated with hsTnI (r 0.62, p < 0.05) and IL6 (r 0.881, p < 0.05). Klotho levels were correlated with 6MWT (r 0.57, p < 0.05)., Conclusions: While inflammatory biomarkers were correlated with cardiac function, klotho levels were associated with clinical performance in the population with TTR-CA., Competing Interests: The authors declare no conflicts of interest.

Background : Acute cardiac injury (ACI) after COVID-19 has been linked with unfavorable clinical outcomes, but data on the clinical impact of elevated cardiac troponin on discharge during follow-up are scarce. Our objective is to elucidate the clinical outcome of patients with elevated troponin on discharge after surviving a COVID-19 hospitalization. Methods : We conducted an analysis in the prospective registry HOPE-2 (NCT04778020). Only patients discharged alive were selected for analysis, and all-cause death on follow-up was considered as the primary endpoint. As a secondary endpoint, we established any long-term COVID-19 symptoms. HOPE-2 stopped enrolling patients on 31 December 2021, with 9299 patients hospitalized with COVID-19, of which 1805 were deceased during the acute phase. Finally, 2382 patients alive on discharge underwent propensity score matching by relevant baseline variables in a 1:3 fashion, from 56 centers in 8 countries. Results : Patients with elevated troponin experienced significantly higher all-cause death during follow-up (log-rank = 27.23, p < 0.001), and had a higher chance of experiencing long-term COVID-19 cardiovascular symptoms. Specifically, fatigue and dyspnea (57.7% and 62.8%, with p -values of 0.009 and <0.001, respectively) are among the most common. Conclusions: After surviving the acute phase, patients with elevated troponin on discharge present increased mortality and long-term COVID-19 symptoms over time, which is clinically relevant in follow-up visits.

Background: Cancer-therapy-related cardiac dysfunction (CTRCD) is a growing concern for public health, with a growing incidence due to improved survival rates of patients with hematological malignancies due to diagnostic and therapeutic advances. The identification of patients at risk for CTRCD is vital to developing preventive strategies., Methods: A single-center retrospective cohort study was conducted between 1 January 2017 and 15 February 2023. Medical records of patients with lymphoma treated with first-line anthracyclines were reviewed. Demographic data, cardiovascular risk factors, biomarkers of myocardial damage, and echocardiographic information were collected., Results: A total of 200 patients were included. The incidence of CTRCD was 17.4% (35/200). Patients with CTRCD were older than those without CTRCD, with a mean age of 65.17 years vs. 56.77 ( p = 0.008). Dyslipidemia (DL) (31.4% vs. 13.4% p = 0.017) and previous cardiovascular disease (40% vs. 13.3%; p < 0.001) were more frequent in the group who developed an event. Mean baseline NT-proBNP levels in the subgroup with cardiovascular events were 388.73 kg/L ± 101.02, and they were 251.518 kg/L ± 26.22 in those who did not ( p = 0.004). Differences in Troponin I levels were identified during and after treatment without exceeding the laboratory's upper reference limit. Patients were followed for a median of 51.83 months (0.76-73.49). The presence of a CTCRD event had a negative impact on overall mortality from any cause (HR = 2.23 (95% CI: 1.08-2.93); p = 0.031)., Conclusions: Early identification of risk factors is crucial to manage patients at risk for CTRCD.

The therapeutic management and short-term consequences of the coronavirus disease 2019 (COVID-19) are well known. However, COVID-19 post-acute sequelae are less known and represent a public health problem worldwide. Patients with COVID-19 who present post-acute sequelae may display immune dysregulation, a procoagulant state, and persistent microvascular endotheliopathy that could trigger microvascular thrombosis. These elements have also been implicated in the physiopathology of postural orthostatic tachycardia syndrome, a frequent sequela in post-COVID-19 patients. These mechanisms, directly associated with post-acute sequelae, might determine the thrombotic consequences of COVID-19 and the need for early anticoagulation therapy. In this context, heparin has several potential benefits, including immunomodulatory, anticoagulant, antiviral, pro-endothelial, and vascular effects, that could be helpful in the treatment of COVID-19 post-acute sequelae. In this article, we review the evidence surrounding the post-acute sequelae of COVID-19 and the potential benefits of the use of heparin, with a special focus on the treatment of postural orthostatic tachycardia syndrome.

Objectives: Recently, desert dust in Europe has been recognized as a cardiovascular health problem. In Spain, desert dust inflows in recent years have been associated with worsening air quality. The present study examines whether desert dust events are related to the incidence of acute coronary syndrome (ACS) in patients under 55 years of age. Methods: Data from 2416 consecutive patients admitted to a tertiary hospital due to ACS were prospectively analyzed. A case-crossover time-stratified design using Poisson conditional regression models was applied to estimate the impact of desert dust events involving particulate matter concentrations of an aerodynamic diameter <10 μm (PM 10 ) on the incidence of ACS in patients under 55 years of age. Results: Desert dust intrusion on days 0 to 5 before ACS onset showed no significant association with the incidence of ACS in patients under 55 years of age. The incidence rate ratios of PM 10 concentrations 1, 2, 3, 3, 4, and 5 days before ACS onset (for changes of 10 µg/m 3 ) were 1.02 (95% CI 0.97-1.1; p = 0.41), 1.01 (95% CI 0.96-1.07; p = 0.66), 0.99 (95% CI 0.94-1.05; p = 0.78), 0.96 (95% CI 0.9-1.02; p = 0.18), and 0.97 (95% CI 0.91-1.04; p = 0.41). Conclusions: Our findings suggest that desert dust is unlikely to be related to the incidence of ACS in patients under 55 years of age.

Background: Cardiorespiratory fitness (CRF) is an important component of overall physical fitness and is associated with numerous health benefits, including a reduced risk of heart disease, diabetes, and obesity. However, direct measurement of CRF is time-consuming and therefore not feasible for screening purposes. Methods: A maximal treadmill exercise test with the Bruce protocol was performed to estimate VO 2max in 1047 Spanish men and women aged 17 to 62 years. Weight, height, and heart rate were measured. Leisure-time physical activity (LTPA) was recorded using the Minnesota Leisure Time Physical Activity Questionnaire. A multiple linear regression model was developed to predict exercise-based VO 2max . The validity of the model was examined by correlation, concordance, Bland-Altman analysis, cross-validation, and construct validity analysis. Results: There was no significant difference between VO 2max obtained by the Bruce protocol (43.56 mL/kg/min) or predicted by the equation (43.59 mL/kg/min), with R 2 of 0.57, and a standard error of the estimate of 7.59 mL/kg/min. Pearson's product-moment correlation and Lin's concordance correlation between measured and predicted CRF values were 0.75 and 0.72, respectively. Bland-Altman analysis revealed a significant proportional bias of non-exercise eCRF, overestimating unfit and underestimating highly fit individuals. However, 64.3% of participants were correctly classified into CRF tertile categories, with an important 69.9% in the unfit category. Conclusions: The eCRF equation was associated with several cardiovascular risk factors in the anticipated directions, indicating good construct validity. In conclusion, the non-exercise eCRF showed a reasonable validity to estimate true VO 2max , and it may be a useful tool for screening CRF.

Acute coronary syndromes (ACS), encompassing conditions like ST-elevation myocardial infarction (STEMI) and non-ST-elevation acute coronary syndromes (NSTE-ACS), represent a significant challenge in cardiovascular care due to their complex pathophysiology and substantial impact on morbidity and mortality. The 2023 European Society of Cardiology (ESC) guidelines for ACS management introduce several updates in key areas such as invasive treatment timing in NSTE-ACS, pre-treatment strategies, approaches to multivessel disease, and the use of imaging modalities including computed tomography (CT) coronary angiography, magnetic resonance imaging (MRI), and intracoronary imaging techniques, such as optical coherence tomography (OCT) and intravascular ultrasound (IVUS). They also address a modulation of antiplatelet therapy, taking into consideration different patient risk profiles, and introduce new recommendations for low-dose colchicine. These guidelines provide important evidence-based updates in practice, reflecting an evolution in the understanding and management of ACS, yet some potentially missed opportunities for more personalized care and technology adoption are discussed.

The application of bacterial metagenomic analysis as a biomarker for cancer detection is emerging. Our aim was to discover gut microbiota signatures with potential utility in the diagnosis of colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). A prospective study was performed on a total of 77 fecal samples from CRC and NSCLC patients and controls. DNA from stool was analyzed for bacterial genomic sequencing using the Ion Torrent™ technology. Bioinformatic analysis was performed using the QIIME2 pipeline. We applied logistic regression to adjust for differences attributable to sex, age, and body mass index, and the diagnostic accuracy of our gut signatures was compared with other previously published results. The feces of patients affected by different tumor types, such as CRC and NSCLC, showed a differential intestinal microbiota profile. After adjusting for confounders, Parvimonas (OR = 53.3), Gemella (OR = 6.01), Eisenbergiella (OR = 5.35), Peptostreptococcus (OR = 9.42), Lactobacillus (OR = 6.72), Salmonella (OR = 5.44), and Fusobacterium (OR = 78.9) remained significantly associated with the risk of CRC. Two genera from the Ruminococcaceae family, DTU089 (OR = 20.1) and an uncharacterized genus (OR = 160.1), were associated with the risk of NSCLC. Our two panels had better diagnostic capacity for CRC (AUC = 0.840) and NSLC (AUC = 0.747) compared to the application of two other published panels to our population. Thus, we propose a gut bacteria panel for each cancer type and show its potential application in cancer diagnosis., Competing Interests: The authors declare that there are no conflicts of interests.